{"doi":"10.1038/jid.2013.353","title":"NKG2D Triggers Cytotoxicity in Murine Epidermal γδ T Cells via PI3K-Dependent, Syk/ZAP70-Independent Signaling Pathway","abstract":null,"journal":"Journal of Investigative Dermatology","year":2014,"id":588509,"datarank":1.2037515754653687,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"self_citation_contribution":0.5101796072493234,"citation_network_contribution":0.6935719682160454,"self_endowment_contribution":0.5101796072493234,"citer_contribution":0.6935719682160454,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":25,"citers_with_citation_signal":24,"citers_with_endowment":24,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1505579,"name":"Kazuhiro Kawai","orcid":null,"position":1,"is_corresponding":false},{"id":1505580,"name":"Shigeru Yoshida","orcid":null,"position":2,"is_corresponding":false},{"id":1505581,"name":"Youhei Uchida","orcid":null,"position":3,"is_corresponding":false},{"id":1505582,"name":"Ayano Nitahara-Takeuchi","orcid":null,"position":4,"is_corresponding":false},{"id":947050,"name":"Kimiko Kuroki","orcid":"0000-0001-9796-4217","position":5,"is_corresponding":false},{"id":1505583,"name":"Mizuho Kajikawa","orcid":null,"position":6,"is_corresponding":false},{"id":161237,"name":"Toyoyuki Ose","orcid":null,"position":7,"is_corresponding":false},{"id":947051,"name":"Katsumi Maenaka","orcid":"0000-0002-5459-521X","position":8,"is_corresponding":false},{"id":1505584,"name":"Masanori Kasahara","orcid":null,"position":9,"is_corresponding":false},{"id":159606,"name":"Takuro Kanekura","orcid":null,"position":10,"is_corresponding":false},{"id":1505578,"name":"Atsuko Ibusuki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"NKG2D Triggers Cytotoxicity in Murine Epidermal γδ T Cells via PI3K-Dependent, Syk/ZAP70-Independent Signaling Pathway","abstract":"Murine epidermal γδ T cells, known as dendritic epidermal T cells (DETCs), survey tissue stress through the invariant T-cell receptor (TCR) and non-clonotypic receptors such as NKG2D. NKG2D signaling via the DAP10-phosphatidylinositol 3-kinase (PI3K) pathway directly stimulates cytotoxicity in natural killer (NK) cells and costimulates CD8(+) T cells to augment TCR signals. In activated murine NK cells, NKG2D signals also via the DAP12-Syk/ZAP70 pathway that triggers both cytotoxicity and cytokine production. It remains controversial whether NKG2D on DETCs is a primary activating receptor or functions only as a costimulatory receptor, and signaling pathways initiated by NKG2D ligation in DETCs have not been analyzed. We show that stimulation of short-term DETC lines with recombinant NKG2D ligands triggers degranulation (exocytosis of cytotoxic granules) via the PI3K-dependent signaling pathway, but does not induce cytokine production or Syk/ZAP70 activation. Coengagement of TCR or Syk/ZAP70 signaling was not crucial for DETC-mediated killing of NKG2D ligand-expressing target cells. Thus, NKG2D can function as a coactivating stress receptor that directly triggers cytotoxicity in DETCs, at least after priming, via the PI3K-dependent, Syk/ZAP70-independent signaling pathway.","is_dataset_classified":null,"base_score":3.4011973816621555,"endowment":3.4011973816621555,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"23962808","pmcid":null,"openalex_id":"https://openalex.org/W2057567013","authors":[],"funders":[],"total_grants":0,"fwci":0.8743,"citation_percentile":0.73669953,"influential_citations":1,"citation_trend":[{"year":2015,"count":4},{"year":2016,"count":2},{"year":2017,"count":1},{"year":2018,"count":4},{"year":2020,"count":4},{"year":2021,"count":3},{"year":2022,"count":3},{"year":2024,"count":3},{"year":2025,"count":4},{"year":2026,"count":1}],"oa_status":"bronze","license":"http://www.elsevier.com/open-access/userlicense/1.0/","oa_locations":[{"url":"http://www.jidonline.org/article/S0022202X1536601X/pdf","host_type":"journal"},{"url":"http://www.jidonline.org/article/S0022202X1536601X/pdf","host_type":"BRONZE"},{"url":"http://www.jidonline.org/article/S0022202X1536601X/pdf","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022202X1536601X?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0022202X1536601X?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1038/jid.2013.353","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/23962808","host_type":"repository"}],"fields_of_study":["Immune Cell Function and Interaction","T-cell and B-cell Immunology","CAR-T cell therapy research","Chemistry","Medicine","Biology","Animals","Antibodies, Monoclonal","Cell Line","Cytoplasmic Granules","Epidermal Cells","Epidermis","Exocytosis","Intracellular Signaling Peptides and Proteins","Killer Cells, Natural","Langerhans Cells","Mice","Mice, Inbred C57BL","NK Cell Lectin-Like Receptor Subfamily K","Phosphatidylinositol 3-Kinases","Protein-Tyrosine Kinases","Receptors, Antigen, T-Cell, gamma-delta","Signal Transduction","Syk Kinase","T-Lymphocytes, Cytotoxic","ZAP-70 Protein-Tyrosine Kinase"],"mesh_terms":["Syk Kinase","Epidermal Cells","Animals","Antibodies, Monoclonal","Cell Line","Cytoplasmic Granules","Epidermis","Exocytosis","Killer Cells, Natural","Langerhans Cells","Mice, Inbred C57BL","Protein-Tyrosine Kinases","T-Lymphocytes, Cytotoxic","Signal Transduction","Receptors, Antigen, T-Cell, gamma-delta","Phosphatidylinositol 3-Kinases","Intracellular Signaling Peptides and Proteins","Mice","ZAP-70 Protein-Tyrosine Kinase","NK Cell Lectin-Like Receptor Subfamily K"],"keywords":["NKG2D","Syk","ZAP70","Cell biology","Cytotoxic T cell","Biology","T-cell receptor","CD8","T cell","Degranulation","Signal transduction","Receptor","Immunology","Tyrosine kinase","Immune system","Biochemistry","In vitro"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-21T08:56:02.807414Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}